The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury

Jones, Leonard L.; Margolis, Richard U.; Tuszynski, Mark H.

doi:10.1016/s0014-4886(03)00087-6

Cited by 508 publications

(428 citation statements)

References 44 publications

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“…Furthermore, CSPGs produced by neurons and astrocytes form lattice-like perineuronal nets that shroud adult neuronal cell bodies and proximal dendrites [60,61]. Concentrations of some CSPGs increase in humans and animals not only at the SCI site [62][63][64][65][66][67][68][69][70][71] but also rostral [70] and caudal [72] to it.…”

Section: Pharmacological and Gene-delivery Approachesmentioning

confidence: 99%

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

2011

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Summary: Motor, sensory, and autonomic functions can spontaneously return or recover to varying extents in both humans and animals, regardless of the traumatic spinal cord injury (SCI) level and whether it was complete or incomplete. In parallel, adverse and painful functions can appear. The underlying mechanisms for all of these diverse functional changes are summarized under the term plasticity. Our review will describe what is known regarding this phenomenon after traumatic SCI and focus on its relevance to motor and sensory recovery. Although it is still somewhat speculative, plasticity can be found throughout the neuraxis and includes various changes ranging from alterations in the properties of spared neuronal circuitries, intact or lesioned axon collateral sprouting, and synaptic rearrangements. Furthermore, we will discuss a selection of potential approaches for facilitating plasticity as possible SCI treatments. Because a mechanism underlying spontaneous plasticity and recovery might be motor activity and the related neuronal activity, activity-based therapies are being used and investigated both clinically and experimentally. Additional pharmacological and gene-delivery approaches, based on plasticity being dependent on the delicate balance between growth inhibition and promotion as well as the basic intrinsic growth ability of the neurons themselves, have been found to be effective alone and in combination with activitybased therapies. The positive results have to be tempered with the reality that not all plasticity is beneficial. Therefore, a tremendous number of questions still need to be addressed. Ultimately, answers to these questions will enhance plasticity's potential for improving the quality of life for persons with SCI.

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Section: Pharmacological and Gene-delivery Approachesmentioning

confidence: 99%

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

2011

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“…The primary function of the glial scar is to restore the blood-spinal cord barrier to prevent an overwhelming inflammatory response following SCI (3,4). However, injured axons are unable to regenerate across the site of injury in the central nervous system because of the presence of an array of inhibitory cues present within the scar (For a review, see 5,6), in particular chondroitin sulphate proteoglycans (CSPGs) (7)(8)(9)(10). Digestion of CSPGs with the bacterial enzyme chondroitinase ABC (ChABC), following local delivery to the spinal cord, has led to axon regeneration, plastic neuronal rearrangements and functional recovery following section or crush injury in laboratory animal SCI models (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Canine olfactory ensheathing cells from the olfactory mucosa can be engineered to produce active chondroitinase ABC

Carwardine

Wong

Fawcett

et al. 2016

Journal of the Neurological Sciences

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A multitude of factors must be overcome following spinal cord injury (SCI) in order to achieve clinical improvement in patients. It is thought that by combining promising therapies these diverse factors could be combatted with the aim of producing an overall improvement in function. Chondroitin sulphate proteoglycans (CSPGs) present in the glial scar that forms following SCI present a significant block to axon regeneration. Digestion of CSPGs by chondroitinase ABC (ChABC) leads to axon regeneration, neuronal plasticity and functional improvement in preclinical models of SCI. However, the enzyme activity decays at body temperature within 24-72 hours, limiting the translational potential of ChABC as a therapy. Olfactory ensheathing cells (OECs) have shown huge promise as a cell transplant therapy in SCI. Their beneficial effects have been demonstrated in multiple small animal SCI models as well as in naturally occurring SCI in canine patients. In the present study, we have genetically modified canine OECs from the mucosa to constitutively produce enzymatically active ChABC. We have developed a lentiviral vector that can deliver a mammalian modified version of the ChABC gene to mammalian cells, including OECs. Enzyme production was quantified using the Morgan-Elson assay that detects the breakdown products of CSPG digestion in cell supernatants. We confirmed our findings by immunolabelling cell supernatant samples using Western blotting. OECs normal cell function was unaffected by genetic modification as demonstrated by normal microscopic morphology and the presence of the low affinity neurotrophin receptor (p75 NGF ) following viral transduction. We have developed the means to allow production of active ChABC in combination with a promising cell transplant therapy for SCI repair.

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“…These CSPGs are important to brain structure through maintenance of the correct hydrodynamics and in their interactions with other ECM components. They also contribute to disease processes and their synthesis is modulated by injury [14]. As a group, CSPGs are known to inhibit neurite outgrowth and axonal regeneration and promote neural cell death [2], [12], [15], [19], [39].…”

Section: Introductionmentioning

confidence: 99%

ADAMTS-1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes

et al. 2006

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ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzymes are a recently described group of metalloproteinases. The substrates degraded by ADAMTS-1, -4 and -5 suggests that they play a role in turnover of extracellular matrix in the central nervous system (CNS). ADAMTS-1 is also known to exhibit anti-angiogenic activity. Their main endogenous inhibitor is tissue inhibitor of metalloproteinases (TIMP)-3.The present study was designed to investigate ADAMTS-1, -4 and -5 and TIMP-3 expression after experimental cerebral ischaemia and to examine whether cytokines known to be up-regulated in stroke could alter their expression by astrocytes in vitro.Focal cerebral ischaemia was induced by transient middle cerebral artery occlusion in the rat using the filament method.Our results demonstrate a significant increase in expression of ADAMTS-1 and -4 in the occluded hemisphere but no significant change in TIMP-3. This was accompanied by an increase in mRNA levels for interleukin (IL)-1β, IL-1 receptor antagonist (IL1ra) and tumour necrosis factor (TNF). ADAMTS-4 mRNA and protein was upregulated by TNF in primary human astrocyte cultures. The increased ADAMTS-1 and -4 in experimental stroke, together with no change in TIMP-3, may promote ECM breakdown after stroke, enabling infiltration of inflammatory cells and contribute to brain injury. In vitro studies suggest that the in vivo modulation of ADAMTS-1 and -4 may be controlled in part by TNF.3

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The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury

Cited by 508 publications

References 44 publications

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

Canine olfactory ensheathing cells from the olfactory mucosa can be engineered to produce active chondroitinase ABC

ADAMTS-1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes

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